JPH0797714A - Production of collagen fiber - Google Patents
Production of collagen fiberInfo
- Publication number
- JPH0797714A JPH0797714A JP6111899A JP11189994A JPH0797714A JP H0797714 A JPH0797714 A JP H0797714A JP 6111899 A JP6111899 A JP 6111899A JP 11189994 A JP11189994 A JP 11189994A JP H0797714 A JPH0797714 A JP H0797714A
- Authority
- JP
- Japan
- Prior art keywords
- collagen
- solution
- aqueous solution
- hemostatic
- solubilized
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Artificial Filaments (AREA)
- Spinning Methods And Devices For Manufacturing Artificial Fibers (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は外科領域でのあらゆる創
傷部に対して迅速かつ有効に適応できる止血材用のコラ
ーゲン繊維の製造法に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a collagen fiber for a hemostatic material which can be rapidly and effectively adapted to any wound in the surgical field.
【０００２】[0002]
【従来の技術】近年、各医療施設で大手術が比較的頻繁
に行われるが、手術中の出血をいかに予防し、また止血
を確実にかつ短時間に行うかが術後の経過を左右する重
要な因子となっている。例えば、外科手術時の止血法と
しては、圧迫法、結紮法、電気凝固法やトロンビンやフ
ィブリン糊法等の生理活性物質の応用等がある。出血点
のはっきりしている動脈性出血に対しては、一般に結紮
法や電気凝固法が用いられ、静脈性出血であれば圧迫だ
けでも充分であり止血は容易である。しかしながら、実
質臓器からの出血や毛細管性出血に対しては、これらの
止血法が効果のない場合があり、肝不全や心臓血管外科
領域で出血傾向にある場合には、特に止血に困難をきた
す。このような場合、出血面に接触させるだけで血液凝
固反応を促進し、速やかに血栓を形成し出血を阻止する
局所吸収止血材が、手術時間を短縮するのみならず、術
後の再出血をも防止し、安全な術後管理にも貢献するの
で効果的である。2. Description of the Related Art In recent years, major surgery is performed relatively frequently at each medical facility. How to prevent bleeding during surgery and how to stop bleeding reliably and in a short time influence the postoperative course. It is an important factor. For example, hemostasis methods during surgery include application of physiologically active substances such as compression method, ligation method, electrocoagulation method, thrombin and fibrin glue method. Ligation or electrocoagulation is generally used for arterial bleeding with a clear bleeding point, and if venous bleeding, compression alone is sufficient and hemostasis is easy. However, these hemostatic methods may not be effective for bleeding from parenchymal organs or capillary bleeding, and it is particularly difficult to stop bleeding in cases of hepatic failure or bleeding tendency in cardiovascular surgery. . In such a case, a locally absorbed hemostatic material that accelerates the blood coagulation reaction just by contacting the bleeding surface, forms a thrombus promptly and prevents bleeding, not only shortens the operation time but also causes re-bleeding after the operation. It is also effective because it also contributes to safe postoperative management.
【０００３】この目的で、酸化セルロースを材料とする
種々の局所止血材が開発され臨床応用されてきたが、安
価であり操作性に優れるという長所を有するものの、生
体由来の材料でないため生体内での吸収が遅く溶血反応
を惹起するという難点があり、近年は、生体由来の蛋白
質であるコラーゲンを用いた局所止血材が、それ自身の
生理活性作用を有することもあって盛んに臨床に応用さ
れるようになった。For this purpose, various local hemostatic agents using oxidized cellulose have been developed and clinically applied. However, although they have the advantages of being inexpensive and excellent in operability, they are not derived from living organisms However, the topical hemostatic agent using collagen, which is a protein derived from the living body, has been widely applied clinically in recent years due to its physiological activity. It became so.
【０００４】現在、実用化されているコラーゲン製局所
止血材には、天然のコラーゲン繊維を微細粉砕してフレ
ーク状にしたものやコラーゲン溶液を凍結乾燥し平板状
のスポンジにしたものがあるが、前者については、フレ
ーク状であるがゆえに血液に流され飛び散るため止血効
果があまり期待できないし、静電気を帯び易く使用の際
に、手やピンセットに付着し易いという操作面での難点
がある。一方、後者については、るが、平板状であるこ
とから複雑な形状の創傷面に対する密着性が十分でな
く、圧迫止血もできなくなるので前者と同様止血効果が
あまり期待できない。Currently available collagen local hemostatic agents include those obtained by finely pulverizing natural collagen fibers into flakes and those obtained by freeze-drying a collagen solution into a flat sponge. The former has a problem in terms of operation in that it cannot be expected to have a hemostatic effect because it is washed by blood and scatters due to its flaky shape, and that it is easily charged with static electricity and easily adheres to a hand or tweezers during use. On the other hand, with regard to the latter, since it has a flat plate shape, it does not have sufficient adhesion to a wound surface having a complicated shape, and pressure hemostasis cannot be performed.
【０００５】かかる欠点を改善するものとして、コラー
ゲンを繊維状に加工した止血材が提案（人工臓器１９巻
３号（１９９０）Ｐ．１２３５〜１２３８）されてい
る。コラーゲンを繊維状に加工する場合には、高濃度の
塩類溶液にて凝固、再生させるのが一般的であるが、こ
のコラーゲンの繊維状物を止血材として使用するために
は、塩類を十分に除去しておく必要がある。コラーゲン
の再生繊維を洗浄する方法としては、例えば、グルタル
アルデヒド等の架橋剤にて不溶化した後、水で洗浄する
方法が提案（特開平４−６１８６２号公報）されている
が、架橋剤を用いることでコラーゲンの止血作用を損な
うことが避けられない。したがって、止血作用を維持す
るためには、水溶性のコラーゲン繊維をそのままの状態
で洗浄することが必要であり、例えば、コラーゲン繊維
を大量のメタノールで洗浄する方法が提案（人工臓器１
９巻３号（１９９０）Ｐ．１２３５〜１２３８）されて
いるが、塩類の溶解度が低いために大量のメタノールを
必要とする上に塩類を完全に除去することは困難であ
る。In order to improve such a defect, a hemostatic material obtained by processing collagen into a fibrous shape has been proposed (artificial organ vol.19, No.3 (1990) P.1235-1238). When processing collagen into a fibrous form, it is common to coagulate and regenerate it with a high-concentration salt solution, but in order to use this fibrous substance of collagen as a hemostatic agent, sufficient salt should be added. Must be removed. As a method of washing the regenerated fiber of collagen, for example, a method of insolubilizing with a crosslinking agent such as glutaraldehyde and then washing with water has been proposed (JP-A-4-61862), but a crosslinking agent is used. This inevitably impairs the hemostatic effect of collagen. Therefore, in order to maintain the hemostatic effect, it is necessary to wash the water-soluble collagen fiber as it is. For example, a method of washing the collagen fiber with a large amount of methanol is proposed (artificial organ 1
Volume 9, Issue 3 (1990) P. However, since the solubility of salts is low, a large amount of methanol is required and it is difficult to completely remove the salts.
【０００６】一方、コラーゲン繊維を止血材として使用
する場合、止血作用を十分に発揮させるためには、その
繊維形状が均一であることが必要（人工臓器２２巻２号
（１９９３）Ｐ．３４８〜３５２）であり、そのために
は、安定した紡糸法を見い出すことが重要である。On the other hand, when collagen fibers are used as a hemostatic material, the fiber shape must be uniform in order to fully exert the hemostatic effect (Artificial Organ 22 Vol. 2 (1993) P.348-). 352), and for that purpose, it is important to find a stable spinning method.
【０００７】[0007]
【発明が解決しようとする課題】本発明は、コラーゲン
を繊維状にした止血材が実用化されていない原因が、製
造上の問題にあることに鑑み、特に紡糸及び洗浄におけ
る問題点を解決したものであり、本発明の目的は、止血
材としての止血能を十分発揮し、かつ止血処置時の操作
性を向上させ、外科領域におけるあらゆる創傷部に対し
て迅速で有効に対応できる残留塩の少ない止血材用のコ
ラーゲン繊維を得ることにある。DISCLOSURE OF THE INVENTION The present invention has solved the problems particularly in spinning and washing in view of the fact that the reason why a hemostatic material made of fibrous collagen has not been put into practical use is a manufacturing problem. The object of the present invention is to provide a hemostatic ability as a hemostatic material sufficiently, and to improve the operability during hemostatic treatment, and to provide a residual salt that can be rapidly and effectively dealt with for all wounds in the surgical field. To obtain a small amount of collagen fibers for a hemostatic material.
【０００８】[0008]
【課題を解決するための手段】本発明は、可溶化コラー
ゲンを再生してコラーゲン繊維を製造するに際し、可溶
化コラーゲンの酸性溶液を濃厚塩類水溶液中に紡糸口金
より吐出させて凝固、再生したコラーゲン糸条物を、３
０〜９０ｖｏｌ％のアルコールを含む水で温度１０〜４
０℃で洗浄することを特徴とするコラーゲン繊維の製造
法にある。Means for Solving the Problems In the present invention, when solubilized collagen is regenerated to produce collagen fibers, an acidic solution of solubilized collagen is discharged from a spinneret into a concentrated salt solution and coagulated and regenerated. 3 yarns
Water containing 0-90 vol% alcohol temperature 10-4
A method for producing collagen fibers is characterized by washing at 0 ° C.
【０００９】更に、この方法において、好ましくはコラ
ーゲン濃度０．５〜１０ｗｔ％、ｐＨ１．５〜５．０及
び温度０〜３５℃の可溶化コラーゲン塩酸酸性水溶液
を、塩化ナトリウム、塩化カリウム、塩化アンモニウ
ム、硫酸ナトリウム及び硫酸アンモニウムの群から選ば
れる少なくとも一つの塩の水溶液で、飽和溶液濃度に対
する６０％以上の濃度で、かつ温度１０〜４０℃の濃厚
塩類水溶液中に紡糸用口金より吐出させて凝固、再生し
たコラーゲン糸条物を、３０〜９０ｖｏｌ％のイソプロ
パノールを含む水で温度１０〜４０℃で洗浄する方法に
ある。Further, in this method, preferably, a solubilized collagen hydrochloric acid acidic aqueous solution having a collagen concentration of 0.5 to 10 wt%, a pH of 1.5 to 5.0 and a temperature of 0 to 35 ° C. is treated with sodium chloride, potassium chloride or ammonium chloride. , An aqueous solution of at least one salt selected from the group consisting of sodium sulfate and ammonium sulfate, at a concentration of 60% or more with respect to the saturated solution concentration, and discharged from a spinneret into a concentrated salt aqueous solution at a temperature of 10 to 40 ° C. to coagulate, It is a method of washing the regenerated collagen thread with water containing 30 to 90 vol% isopropanol at a temperature of 10 to 40 ° C.
【００１０】本発明において用いるコラーゲンは、繊維
状に再生可能なものであれば特に限定はなく、酸、アル
カリ、酵素等の処理によって不溶性コラーゲンを可溶化
したコラーゲンであるが、可溶化の際、コラーゲンの抗
原性発現部位であるテロペプチドを除去し免疫毒性を低
下させた、酵素処理またはアルカリ処理により可溶化し
た、いわゆるアテロコラーゲンであることが好ましい。The collagen used in the present invention is not particularly limited as long as it can be regenerated into a fibrous form. Insoluble collagen is solubilized by treatment with acid, alkali, enzyme or the like. It is preferable to use so-called atelocollagen which is obtained by removing the telopeptide which is the antigenic expression site of collagen to reduce immunotoxicity, and solubilized by enzyme treatment or alkali treatment.
【００１１】本発明においては、可溶化コラーゲンを酸
性水溶液に溶解して可溶化コラーゲンの酸性溶液とし、
このコラーゲン溶液を紡糸用原液（ドープ）として、濃
厚塩類水溶液からなる紡糸浴中に紡糸用口金よりギヤポ
ンプを用いて一定量ずつ吐出させ紡糸するが、この場合
ドープと紡糸浴とが繊維形成化を行うにあたって重要な
ポイントとなる。In the present invention, solubilized collagen is dissolved in an acidic aqueous solution to obtain an acidic solution of solubilized collagen,
This collagen solution is used as a stock solution for spinning (dope), and a fixed amount of the solution is spun from a spinneret into a spinning bath consisting of an aqueous concentrated salt solution, and spinning is carried out. This is an important point for doing this.
【００１２】コラーゲン溶液は、適度の濃度で、均一で
あることが必要であり、コラーゲン濃度が高すぎると、
粘度が高くなり使用し難くなり、また低すぎると、紡糸
性を損なうことから、溶液のコラーゲン濃度を、０．５
〜１０ｗｔ％とすることが好ましく、より好ましくは
１．０〜５．０ｗｔ％とする。可溶化コラーゲンは、等
電点以下のｐＨでは、分解することなく溶解できるが、
均一な酸性溶液を簡便に得るためには、溶液のｐＨを、
１．５〜５．０とすることが好ましく、安全性と洗浄の
容易さから塩酸による酸性溶液とするのが好ましい。ま
た、可溶化コラーゲンは、溶液状態では、熱変性し易い
ため、溶液温度を、０〜３５℃とすることが好ましい。The collagen solution needs to have a proper concentration and be uniform, and if the collagen concentration is too high,
If the viscosity is high and it is difficult to use, and if it is too low, the spinnability is impaired.
It is preferably set to 10 to 10 wt%, and more preferably 1.0 to 5.0 wt%. Solubilized collagen can be dissolved without decomposition at a pH below the isoelectric point,
To easily obtain a uniform acidic solution, adjust the pH of the solution to
It is preferably 1.5 to 5.0, and an acidic solution with hydrochloric acid is preferable from the viewpoint of safety and ease of washing. In addition, since the solubilized collagen easily undergoes thermal denaturation in a solution state, the solution temperature is preferably 0 to 35 ° C.
【００１３】本発明においては、濃厚塩類水溶液を紡糸
浴として用いるが、濃厚塩類水溶液は、コラーゲンの凝
固性、安全性から、塩類として、塩化ナトリウム、塩化
カリウム、塩化アンモニウム、硫酸ナトリウム及び硫酸
アンモニウムが好ましく用いられ、かかる群から選ばれ
る少なくとも一つの塩の、その飽和溶液濃度に対する６
０％以上の濃度の濃厚塩類水溶液とすることが好まし
く、濃厚塩類水溶液でないと、コラーゲンの凝固、再生
に時間がかかり、高速で安定した紡糸を行うことが困難
となる。また、濃厚塩類水溶液は、高温では、コラーゲ
ンの熱変性が促進されるので、温度１０〜４０℃とする
ことが好ましい。In the present invention, a concentrated salt aqueous solution is used as a spinning bath, but sodium chloride, potassium chloride, ammonium chloride, sodium sulfate and ammonium sulfate are preferable as the salt because of the coagulation property and safety of collagen. 6 of at least one salt used and selected from such group, relative to its saturated solution concentration
It is preferable to use a concentrated salt aqueous solution having a concentration of 0% or more. If it is not a concentrated salt aqueous solution, it takes time to coagulate and regenerate collagen, and it becomes difficult to perform stable spinning at high speed. Further, the temperature of the concentrated salt aqueous solution is preferably 10 to 40 ° C. because the thermal denaturation of collagen is promoted at high temperatures.
【００１４】また、繊維の製造に当たっては、紡糸口金
からのドープの吐出量と紡糸の捲取りローラー速度比に
よって凝固、再生及び繊維の太さが決定され、必要によ
り第２浴以降複数の紡糸浴で延伸、再生等が強化され繊
維形成化の充実と糸物性の向上を図ることもできる。Further, in the production of fibers, the coagulation, regeneration and fiber thickness are determined by the discharge amount of the dope from the spinneret and the speed ratio of the take-up roller for spinning, and if necessary, a plurality of spinning baths after the second bath are used. By so doing, stretching and recycling can be strengthened to enhance fiber formation and improve yarn physical properties.
【００１５】紡糸浴で凝固、再生したコラーゲン糸条物
は、高濃度の塩類を含有したゲル状の形態をしているの
で、塩類及びその他コラーゲン以外の不純物を除去する
洗浄、精製を行い、乾燥する必要がある。塩類の除去に
対して最も有効な洗浄剤は、水が工業的な面でも優れて
いるが、可溶化コラーゲンは本来水に溶解するので、再
生したコラーゲン糸条物に対して水を洗浄剤として単独
で使用することができない。本発明においては、コラー
ゲン糸条物を溶解しない範囲で、可溶化コラーゲンの非
溶剤のアルコールと水との混合溶液とし、洗浄剤として
用いることが塩類の除去に極めて有効であることを見い
だしたものである。Since the collagen filaments coagulated and regenerated in the spinning bath are in the form of gel containing a high concentration of salts, they are washed, purified to remove salts and other impurities other than collagen, and dried. There is a need to. The most effective detergent for removing salts is water, which is excellent in terms of industry, but solubilized collagen is originally soluble in water, so water is used as a detergent for regenerated collagen yarn. It cannot be used alone. In the present invention, it has been found that it is extremely effective to remove salts by forming a mixed solution of solubilized collagen with a non-solvent alcohol and water in a range that does not dissolve collagen yarn. Is.
【００１６】可溶化コラーゲンの非溶剤で、かつ水と混
合溶液を作り得る有機溶剤としては、アルコール、ケト
ン、エーテル等が挙げられるが、本発明においては、取
扱い性の点からアルコールを用いる。アルコールには、
メタノール、エタノール、イソプロパノール、ｎ−プロ
パノール、ｎ−ブタノール、イソブタノール、ｓｅｃ−
ブタノール、ｔｅｒｔ−ブタノール等が挙げられるが、
特に医療用品の製造において使用する場合、安全性及び
製造コストを考慮し、更に製造プロセス上最適な物性を
備えたアルコールとして、イソプロパノールが好ましく
用いられる。Examples of the organic solvent which is a non-solvent for solubilized collagen and which can form a mixed solution with water include alcohols, ketones and ethers. In the present invention, alcohol is used from the viewpoint of handleability. For alcohol,
Methanol, ethanol, isopropanol, n-propanol, n-butanol, isobutanol, sec-
Butanol, tert-butanol and the like can be mentioned,
In particular, when used in the production of medical supplies, isopropanol is preferably used as an alcohol having optimum physical properties in the production process in consideration of safety and production cost.
【００１７】本発明における洗浄でのアルコールと水と
の混合比率は、塩類の洗浄効果は、アルコールの比率が
高いほど低下するので、コラーゲン糸条物を溶解しない
範囲で出来るだけ水の比率を高くし、アルコール３０〜
９０ｖｏｌ％、水７０〜１０ｖｏｌ％とすることが好ま
しい。また、コラーゲン糸条物は、洗浄により塩類が除
去されるに従って溶解され易くなるため、洗浄の進行と
共にアルコールの混合比率を徐々に高めることが好まし
い。また、洗浄は、その洗浄効果を高めるために出来る
だけ高い温度で行うことが好ましいが、コラーゲンの熱
変性を防止することを含めて、洗浄は、温度１０〜４０
℃で実施する。As for the mixing ratio of alcohol and water in the washing in the present invention, the washing effect of salts decreases as the proportion of alcohol decreases, so that the proportion of water should be as high as possible within the range in which collagen thread is not dissolved. Alcohol 30 ~
90 vol% and 70 to 10 vol% of water are preferable. In addition, the collagen thread is more likely to be dissolved as salts are removed by washing, and therefore it is preferable to gradually increase the mixing ratio of alcohol as the washing progresses. The washing is preferably performed at a temperature as high as possible in order to enhance the washing effect, but the washing is performed at a temperature of 10 to 40 including prevention of thermal denaturation of collagen.
Carry out at ° C.
【００１８】以上のような方法で得られたコラーゲン糸
条物は、有機溶剤により脱水した後、乾燥し、必要によ
り架橋処理、滅菌処理を行うことによって、取扱い性と
生体吸収性の高い、優れた止血材となすことができる。The collagen thread obtained by the above method is dehydrated with an organic solvent, dried, and optionally subjected to a crosslinking treatment and a sterilization treatment so that it has high handleability and bioabsorbability, and is excellent. It can be used as a hemostatic material.
【００１９】[0019]
【実施例】以下、本発明を実施例により具体的に説明す
る。なお、実施例中、止血時間、塩含有量、風合い、止
血能は、次の評価に従った。EXAMPLES The present invention will be specifically described below with reference to examples. In the examples, the hemostatic time, salt content, texture, and hemostatic ability were according to the following evaluation.
【００２０】塩含有量： 厚生省基準値０．０５４ｗｔ％以下 風合い（皮膚接触性）： 柔軟から硬いまでの順に５、４、３、２、１で表示 止血時間： 犬の脾臓皮膜を剥離し出血させた後得られたコラーゲン
繊維を止血に供したときの止血時間（分）を測定 止血能： 以下のＡ、Ｂ、Ｃで表示 Ａ １分以内に止血が完了 Ｂ ３分以内に止血が完了 Ｃ ５分以内に止血が完了Salt content: Ministry of Health and Welfare standard value 0.054 wt% or less Texture (skin contact): Shown in the order of 5, 4, 3, 2, 1 from soft to hard Hemostasis time: Peeling the spleen coat of dogs and bleeding Measure the hemostasis time (minutes) when the collagen fiber obtained after being subjected to hemostasis Hemostasis ability: Displayed as A, B, and C below A Hemostasis completed within 1 minute B Hemostasis completed within 3 minutes C Hemostasis completed within 5 minutes
【００２１】（実施例１）新鮮牛皮より得られた不溶性
コラーゲンを蛋白質分解酵素ペプシンで分解処理し、得
られたアテロコラーゲンを塩酸水溶液を用いて、表１に
示したような、コラーゲン濃度、ｐＨ及び温度の異なる
ドープを調製した。(Example 1) Insoluble collagen obtained from fresh cowhide was decomposed with proteolytic enzyme pepsin, and the obtained atelocollagen was treated with an aqueous hydrochloric acid solution to obtain the collagen concentration, pH and Dopes with different temperatures were prepared.
【００２２】このドープを、ギヤポンプでノズル径１０
０μｍ、５００ホールの紡糸口金より２５℃の２５ｗｔ
％塩化アンモニウム水溶液の紡糸浴中に吐出し、紡糸度
１０〜１５ｍ／ｍｉｎで紡糸し、捲取った。得られたコ
ラーゲン糸条物を、イソプロパノール５０ｖｏｌ％を含
有する水で３０℃で洗浄し、更にイソプロパノールで脱
水した後室温で風乾した。得られたコラーゲン繊維の性
状及びコラーゲン繊維での止血時間を表１に示した。い
ずれの条件においても得られたコラーゲン繊維は、止血
材として使用可能であったが、本発明の製造条件（Ｎ
ｏ．１〜３）で良好に製造され、良好な繊維物性を有し
ていた。This dope was sprayed with a gear pump at a nozzle diameter of 10
25 wt at 25 ° C from 0 μm, 500 hole spinneret
% Ammonium chloride aqueous solution was discharged into a spinning bath, spun at a spinning degree of 10 to 15 m / min, and wound. The obtained collagen thread was washed with water containing 50 vol% of isopropanol at 30 ° C., dehydrated with isopropanol, and then air dried at room temperature. Table 1 shows the properties of the obtained collagen fibers and the hemostasis time of the collagen fibers. The collagen fibers obtained under any of the conditions could be used as a hemostatic material, but the production conditions (N
o. 1 to 3), and had good fiber physical properties.
【００２３】[0023]
【表１】 [Table 1]
【００２４】（実施例２）実施例１Ｎｏ．２で用いたと
同じドープを用い、表２に示したような、塩類、濃度及
び温度の異なる第１紡糸浴を用い、更に第２紡糸浴を用
いた以外は、実施例１と同様にしてコラーゲン繊維を得
た。得られたコラーゲン繊維の性状及びコラーゲン繊維
での止血時間を表２に示した。いずれの条件においても
得られたコラーゲン繊維は、止血材として使用可能であ
ったが、本発明の製造条件（Ｎｏ．１０〜１２及びＮ
ｏ．１６〜２２）で良好に製造され、良好な繊維物性を
有していた。Example 2 Example 1 No. Collagen as in Example 1 except that the same dope as used in Example 2 was used, the first spinning bath with different salts, concentration and temperature as shown in Table 2 was used, and the second spinning bath was further used. Fiber was obtained. The properties of the obtained collagen fibers and the hemostasis time of the collagen fibers are shown in Table 2. The collagen fibers obtained under any of the conditions were usable as a hemostatic material, but the production conditions of the present invention (No. 10 to 12 and N
o. 16 to 22), and had good fiber physical properties.
【００２５】[0025]
【表２】 [Table 2]
【００２６】（実施例３）実施例１において、洗浄条件
を表３に示す洗浄条件（Ｎｏ．２１〜２４）に代えた以
外は、実施例１Ｎｏ．２と同様にしてコラーゲン繊維を
得た。得られたコラーゲン繊維の塩含有量、風合い及び
止血能を表５に示した。本発明の製造条件によれば短時
間で効率的に洗浄されていた。(Example 3) Example 1 No. 1 except that the cleaning conditions in Example 1 were changed to the cleaning conditions (Nos. 21 to 24) shown in Table 3. Collagen fibers were obtained in the same manner as in 2. Table 5 shows the salt content, texture and hemostatic ability of the obtained collagen fibers. According to the manufacturing conditions of the present invention, the cleaning was performed efficiently in a short time.
【００２７】[0027]
【表３】 [Table 3]
【００２８】（実施例４）実施例１において、コラーゲ
ンをアルカリ処理して得られたアテロコラーゲン（Ｎ
ｏ．２５）に代えた以外は、実施例１Ｎｏ．１と同様に
してコラーゲン繊維を得た。得られたコラーゲン繊維の
塩含有量、風合い及び止血能を表５に示した。本発明の
製造条件によれば短時間で効率的に洗浄されていた。Example 4 Atelocollagen (N
o. No. 25) except that Example 1 No. A collagen fiber was obtained in the same manner as in 1. Table 5 shows the salt content, texture and hemostatic ability of the obtained collagen fibers. According to the manufacturing conditions of the present invention, the cleaning was performed efficiently in a short time.
【００２９】（比較例１）実施例１において、洗浄条件
を表４に示す洗浄条件（Ｎｏ．２６〜３１）に代えた以
外は、実施例１Ｎｏ．２と同様にしてコラーゲン繊維を
得た。得られたコラーゲン繊維の塩含有量、風合い及び
止血能を表５に示した。(Comparative Example 1) Example 1 No. 1 except that the cleaning conditions in Example 1 were changed to the cleaning conditions (Nos. 26 to 31) shown in Table 4. Collagen fibers were obtained in the same manner as in 2. Table 5 shows the salt content, texture and hemostatic ability of the obtained collagen fibers.
【００３０】[0030]
【表４】 [Table 4]
【００３１】（比較例２）実施例１において、洗浄液を
メタノール（Ｎｏ．３２）に代えた以外は、実施例１Ｎ
ｏ．１と同様にしてコラーゲン繊維を得た。得られたコ
ラーゲン繊維の塩含有量、風合い及び止血能を表５に示
した。(Comparative Example 2) Example 1N except that the cleaning liquid in Example 1 was changed to methanol (No. 32).
o. A collagen fiber was obtained in the same manner as in 1. Table 5 shows the salt content, texture and hemostatic ability of the obtained collagen fibers.
【００３２】（比較例３）実施例１において、洗浄前の
コラーゲン糸条物を０．５ｗｔ％グルタルアルデヒド水
溶液で架橋した後、洗浄に水（Ｎｏ．３３）を用いた以
外は、実施例１Ｎｏ．１と同様にしてコラーゲン繊維を
得た。得られたコラーゲン繊維の塩含有量、風合い及び
止血能を表５に示した。(Comparative Example 3) Example 3 No. 1 except that water (No. 33) was used for washing after cross-linking the collagen thread before washing with a 0.5 wt% glutaraldehyde aqueous solution. ． A collagen fiber was obtained in the same manner as in 1. Table 5 shows the salt content, texture and hemostatic ability of the obtained collagen fibers.
【００３３】[0033]
【表５】 [Table 5]
【００３４】[0034]
【発明の効果】本発明によれば、得られるコラーゲン繊
維は、安定に紡糸法により得られ、かつ紡糸の際の残留
塩類及びコラーゲン以外の不純物が十分に除去されてい
て異物が極めて少なく、しかも生理活性作用を有し、止
血能が高く、止血処置の取扱い性に優れた止血材の材料
として好適なるものである。According to the present invention, the obtained collagen fiber is stably obtained by the spinning method, and the residual salts during spinning and impurities other than collagen are sufficiently removed, and the foreign matter is extremely small, and It is suitable as a hemostatic material having a physiologically active action, a high hemostatic ability, and excellent handleability for hemostatic treatment.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 小谷 修 愛知県名古屋市東区砂田橋四丁目１番60号 三菱レイヨン株式会社商品開発研究所内 (72)発明者 瀧川 高志 愛知県名古屋市東区砂田橋四丁目１番60号 三菱レイヨン株式会社商品開発研究所内 (72)発明者 榊原 巨規 東京都中央区京橋二丁目３番19号 三菱レ イヨン株式会社内 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Osamu Otani 4-chome, Sunadabashi, Higashi-ku, Nagoya, Aichi Prefecture 60-58, Product Development Laboratory, Mitsubishi Rayon Co., Ltd. (72) Takashi Takigawa 4-chome, Sunadabashi, Higashi-ku, Nagoya, Aichi Prefecture No. 60, Product Development Laboratory, Mitsubishi Rayon Co., Ltd. (72) Inventor, Daiki Sakakibara 2-3-19, Kyobashi, Chuo-ku, Tokyo Inside Mitsubishi Rayon Co., Ltd.
Claims (5)
繊維を製造するに際し、可溶化コラーゲンの酸性溶液を
濃厚塩類水溶液中に紡糸口金より吐出させて凝固、再生
したコラーゲン糸条物を、３０〜９０ｖｏｌ％のアルコ
ールを含む水で温度１０〜４０℃で洗浄することを特徴
とするコラーゲン繊維の製造法。1. When the solubilized collagen is regenerated to produce collagen fibers, an acidic solution of solubilized collagen is discharged from a spinneret into a concentrated salt aqueous solution to coagulate and regenerate the collagen filaments in an amount of 30 to 90 vol. A method for producing collagen fibers, which comprises washing with water containing 10% alcohol at a temperature of 10 to 40 ° C.
用いる請求項１記載のコラーゲン繊維の製造法。2. The method for producing collagen fibers according to claim 1, wherein isopropanol is used as the alcohol.
はアルカリ処理によるアテロコラーゲンを用いる請求項
１または請求項２記載のコラーゲン繊維の製造法。3. The method for producing a collagen fiber according to claim 1, wherein atelocollagen treated with an enzyme or an alkali is used as the solubilized collagen.
ゲン濃度０．５〜１０ｗｔ％、ｐＨ１．５〜５．０及び
温度０〜３５℃の塩酸酸性溶液である請求項１、請求項
２または請求項３記載のコラーゲン繊維の製造法。4. The acidic solution of solubilized collagen is a hydrochloric acid acidic solution having a collagen concentration of 0.5 to 10 wt%, a pH of 1.5 to 5.0 and a temperature of 0 to 35 ° C. Item 4. A method for producing a collagen fiber according to Item 3.
化カリウム、塩化アンモニウム、硫酸ナトリウム及び硫
酸アンモニウムの群から選ばれる少なくとも一つの塩の
水溶液で、飽和溶液濃度に対する６０％以上の濃度で、
かつ温度１０〜４０℃の水溶液である請求項１、請求項
２、請求項３または請求項４記載のコラーゲン繊維の製
造法。5. The concentrated salt aqueous solution is an aqueous solution of at least one salt selected from the group consisting of sodium chloride, potassium chloride, ammonium chloride, sodium sulfate and ammonium sulfate, and has a concentration of 60% or more based on the saturated solution concentration.
A method for producing collagen fibers according to claim 1, claim 2, claim 3 or claim 4, which is an aqueous solution having a temperature of 10 to 40 ° C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6111899A JPH0797714A (en) | 1993-05-06 | 1994-04-28 | Production of collagen fiber |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5-127789 | 1993-05-06 | ||
| JP12778993 | 1993-05-06 | ||
| JP6111899A JPH0797714A (en) | 1993-05-06 | 1994-04-28 | Production of collagen fiber |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0797714A true JPH0797714A (en) | 1995-04-11 |
Family
ID=26451195
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6111899A Pending JPH0797714A (en) | 1993-05-06 | 1994-04-28 | Production of collagen fiber |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0797714A (en) |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005100655A1 (en) * | 2004-04-10 | 2005-10-27 | Liwen Zhang | Yarn of leather collagen fiber and the process thereof |
| US7011829B2 (en) | 2001-05-18 | 2006-03-14 | Kanemaru Shin-Ichi | Tissue filler |
| WO2006026899A1 (en) * | 2004-09-09 | 2006-03-16 | Lijin Liu | Yarn of leather and the process thereof |
| JP2009256356A (en) * | 2009-06-01 | 2009-11-05 | Midori Hokuyo Kk | Solubilized collagen fiber, method for producing the same, collagen-containing cosmetic, method for producing the same and production apparatus for solubilized collagen fiber |
| US7615373B2 (en) | 1999-02-25 | 2009-11-10 | Virginia Commonwealth University Intellectual Property Foundation | Electroprocessed collagen and tissue engineering |
| US7759082B2 (en) | 1999-02-25 | 2010-07-20 | Virginia Commonwealth University Intellectual Property Foundation | Electroprocessed fibrin-based matrices and tissues |
| WO2011064773A1 (en) * | 2009-11-24 | 2011-06-03 | Collplant Ltd. | Method of generating collagen fibers |
| JP2015200055A (en) * | 2014-04-01 | 2015-11-12 | 兵庫県 | Method of producing collagen fiber and method of producing high-concentration collagen solution |
| WO2019157866A1 (en) * | 2018-02-13 | 2019-08-22 | 韩宏宇 | Collagen fiber composite yarn, preparation method therefor, use thereof, and textile article |
| US10716876B2 (en) | 2017-01-12 | 2020-07-21 | Collplant Ltd. | Method of generating collagen fibers |
| WO2020162626A1 (en) * | 2019-02-07 | 2020-08-13 | Ｓｐｉｂｅｒ株式会社 | Recombinant-structure protein multifilament and method for manufacturing same |
| CN115434019A (en) * | 2022-10-21 | 2022-12-06 | 辛集市梅花皮业有限公司 | Spinning system for collagen fibers |
-
1994
- 1994-04-28 JP JP6111899A patent/JPH0797714A/en active Pending
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7615373B2 (en) | 1999-02-25 | 2009-11-10 | Virginia Commonwealth University Intellectual Property Foundation | Electroprocessed collagen and tissue engineering |
| US7759082B2 (en) | 1999-02-25 | 2010-07-20 | Virginia Commonwealth University Intellectual Property Foundation | Electroprocessed fibrin-based matrices and tissues |
| US7011829B2 (en) | 2001-05-18 | 2006-03-14 | Kanemaru Shin-Ichi | Tissue filler |
| US8328878B2 (en) | 2004-04-10 | 2012-12-11 | Liwen Zhang | Yarn of animal collagen fiber and manufacture process thereof |
| JP2007532786A (en) * | 2004-04-10 | 2007-11-15 | 立文 張 | Animal leather collagen fiber system and production method thereof |
| WO2005100655A1 (en) * | 2004-04-10 | 2005-10-27 | Liwen Zhang | Yarn of leather collagen fiber and the process thereof |
| WO2006026899A1 (en) * | 2004-09-09 | 2006-03-16 | Lijin Liu | Yarn of leather and the process thereof |
| JP2009256356A (en) * | 2009-06-01 | 2009-11-05 | Midori Hokuyo Kk | Solubilized collagen fiber, method for producing the same, collagen-containing cosmetic, method for producing the same and production apparatus for solubilized collagen fiber |
| WO2011064773A1 (en) * | 2009-11-24 | 2011-06-03 | Collplant Ltd. | Method of generating collagen fibers |
| JP2015200055A (en) * | 2014-04-01 | 2015-11-12 | 兵庫県 | Method of producing collagen fiber and method of producing high-concentration collagen solution |
| US10716876B2 (en) | 2017-01-12 | 2020-07-21 | Collplant Ltd. | Method of generating collagen fibers |
| WO2019157866A1 (en) * | 2018-02-13 | 2019-08-22 | 韩宏宇 | Collagen fiber composite yarn, preparation method therefor, use thereof, and textile article |
| WO2020162626A1 (en) * | 2019-02-07 | 2020-08-13 | Ｓｐｉｂｅｒ株式会社 | Recombinant-structure protein multifilament and method for manufacturing same |
| CN113692460A (en) * | 2019-02-07 | 2021-11-23 | 丝芭博株式会社 | Recombinant structural protein multifilament and process for producing the same |
| CN113692460B (en) * | 2019-02-07 | 2024-04-26 | 丝芭博株式会社 | Recombinant structural protein multifilament yarn and method for producing the same |
| CN115434019A (en) * | 2022-10-21 | 2022-12-06 | 辛集市梅花皮业有限公司 | Spinning system for collagen fibers |
| CN115434019B (en) * | 2022-10-21 | 2023-11-10 | 辛集市梅花皮业有限公司 | Spinning system for collagen fibers |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8021684B2 (en) | Haemostatic composition comprising hyaluronic acid | |
| AU677118B2 (en) | Calcium-modified oxidized cellulose hemostat | |
| EP1172115B1 (en) | Hemostatic soluble cellulose fibers containing coagulating protein for treating wound and process for producing the same | |
| EP0468797B1 (en) | Wound dressing material | |
| JP4823476B2 (en) | Hemostasis wound dressing and method for making the same | |
| JPH0797714A (en) | Production of collagen fiber | |
| US9861722B2 (en) | Method for preparing oxidized cellulose hemostatic product | |
| CA2033046C (en) | Process for preparing a neutralized oxidized cellulose product and its method of use | |
| KR101735899B1 (en) | Biodegradable non-woven material for medical purposes | |
| US5679372A (en) | Absorbable topical hemostat | |
| JPH0835193A (en) | Production of collagen fiber nonwoven fabric sheet | |
| JPH0461862A (en) | Collagen fiber hemostatic material and its manufacture | |
| CN112996820A (en) | Cellulose-containing material | |
| JP3086822B1 (en) | Gelatin fiber, method for producing the same, gelatin fiber aggregate, and bioabsorbable material | |
| JP3948623B2 (en) | Gelatin-coated alginate fiber and method for producing the same | |
| KR20010074825A (en) | Topically Absorbent Hemostatic Material | |
| JP2003336127A (en) | Conjugated fiber | |
| JPH05209318A (en) | Calcium alginate fiber having excellent liquid absorbing property and covering material for medical use | |
| JPH10508348A (en) | Alginate rope, manufacturing method and application | |
| CN108939136B (en) | Dressing for nasal filling hemostasis and preparation method thereof | |
| JPS6152872A (en) | Wound covering protective tape | |
| JPH06296673A (en) | Fiber for hemostatic material | |
| JP3404097B2 (en) | Locally absorbable hemostat | |
| JPH0813746B2 (en) | Hemostatic agent | |
| JPH08196614A (en) | Locally absorptive hemostatic agent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060307 |
|
| A977 | Report on retrieval |
Effective date: 20090603 Free format text: JAPANESE INTERMEDIATE CODE: A971007 |
|
| A131 | Notification of reasons for refusal |
Effective date: 20090610 Free format text: JAPANESE INTERMEDIATE CODE: A131 |
|
| A521 | Written amendment |
Effective date: 20090807 Free format text: JAPANESE INTERMEDIATE CODE: A523 |
|
| A131 | Notification of reasons for refusal |
Effective date: 20090902 Free format text: JAPANESE INTERMEDIATE CODE: A131 |
|
| A521 | Written amendment |
Effective date: 20091029 Free format text: JAPANESE INTERMEDIATE CODE: A523 |
|
| A02 | Decision of refusal |
Effective date: 20100602 Free format text: JAPANESE INTERMEDIATE CODE: A02 |